Effects of bovine milk ingestion on urinary excretion of oxypurinol and uric acid.

OBJECTIVE: Although allopurinol is a xanthine oxidase inhibitor, its overall effect may be due to the action of oxypurinol, a metabolite of allopurinol and another xanthine oxidase inhibitor, since the biological half-life of oxypurinol is longer than that of allopurinol. Oxypurinol shares a renal transport pathway with uric acid and ingestion of bovine milk increases the urinary excretion of uric acid. Therefore, we investigated whether its ingestion promotes the urinary excretion of oxypurinol. SUBJECTS/METHODS: Bovine milk (15 ml/kg body weight) was administered to 6 healthy subjects who took allopurinol (300 mg) 12 h prior to ingestion. In addition, a control experiment was performed with the same subjects using the same protocol, except for the ingestion of water instead of bovine milk. Blood and urine samples were collected before and after bovine and water ingestion. RESULTS: In the bovine milk ingestion experiment, the urinary excretion values of oxypurinol and uric acid were increased by 18% and 38%, respectively, and the fractional excretion values of oxypurinol and uric acid were increased by 20% and 40%, respectively, whereas those did not change in the control experiment. In addition, the concentration of alanine and sum of concentrations of amino acids were increased by 16% and 20%, respectively, in the bovine milk ingestion experiment. CONCLUSION: These results suggest that bovine milk ingestion promotes the urinary excretion of oxypurinol as well as uric acid by increasing amino acid concentration.

Serum CRP in patients with gout and effects of benzbromarone.

OBJECTIVE: C-reactive protein (CRP) is associated with increased risk for myocardial infarction, atherosclerosis, and peripheral artery diseases, while increased serum uric acid level is suggested to be independently associated with an increased risk of cardiovascular mortality. Accordingly, to investigate whether hyperuricemia is associated with serum CRP, we compared serum CRP levels between healthy subjects and patients with gout. In addition, we also examined whether benzbromarone has effects on serum CRP levels in patients with gout and the expression of CRP messenger RNA of CRP in the hepatoma cell line HuH7. METHODS: In the first experiment, 40 healthy males and 43 male patients with gout were enrolled, then blood samples were drawn from each after an overnight fast. In the second experiment, 42 male patients with gout were given uric acid-lowering therapy with benzbromarone. Blood samples were drawn after an overnight fast before and 1 year after beginning benzbromarone treatment. In the third experiment, the effects of benzbromarone on IL1beta-induced CRP expression were determined in HuH7 cells. RESULTS: Log serum CRP levels were not significantly different between the patients with gout and healthy subjects, while log serum CRP levels were decreased by 11% after benzbromarone treatment, as compared to the values before treatment (p < 0.01). In addition, log serum adiponectin levels were elevated by 2% after treatment (p < 0.01). Furthermore, our in vitro findings demonstrated that benzbromarone down-regulated IL1beta-stimulated CRP gene expression. CONCLUSIONS: These results suggest that hyperuricemia may not contribute to an increase in serum CRP level, while benzbromarone may have a favorable effect on CRP.

Effects of benzbromarone and allopurinol on adiponectin in vivo and in vitro.

When treating gout patients, we have incidentally found elevated serum levels of adiponectin in some after administration of benzbromarone. In the present study, we determined whether benzbromarone increases the serum level of adiponectin in gout patients and investigated the mechanism involved. Sixty-nine patients with gout were separated into two groups, and then treated for 1 year with uric acid-lowering therapy using benzbromarone or allopurinol. After overnight fasting, blood samples were drawn before and at 1 year after beginning of treatment. In an in vitro study, 3T3L1 cells were incubated in medium containing benzbromarone, allopurinol, pioglitazone, or uric acid, after which real time PCR assays were performed for messenger RNA of adiponectin, aP2, and CD36. Furthermore, 3T3L1 cells were incubated in medium containing GW9662 (PPARgamma antagonist) together with benzbromarone or pioglitazone, after which real-time PCR assays were performed for messenger RNA of adiponectin. In the in vivo study, benzbromarone increased the serum concentration of adiponectin in the subjects, whereas allopurinol did not. In vitro, benzbromarone and pioglitazone each increased the levels of messenger RNA of adiponectin, aP2, and CD36 in 3T3 cells, whereas allopurinol and uric acid did not. Also, GW9662 suppressed the increase in adiponectin mRNA induced by benzbromarone as well as that by pioglitazone. Together, our results suggest that benzbromarone enhances the production of adiponectin via activation of PPARgamma, which is a weak agonist for PPARgamma.

Effect of acarbose on the increased plasma concentration of uric acid induced by sucrose ingestion.

Sucrose is converted fructose and glucose, which may increase plasma uric acid concentration (pUA) through increased purine degradation and/or decreased uric acid (UA) excretion. To investigate effects of acarbose, an inhibitor of alpha-glucosidase, on the increased pUA from sucrose administration, we measured pUA and urinary UA excretion in 6 healthy subjects before and after administering sucrose, with and without co-administration of acarbose. Sucrose raised pUA by 10% (p < 0.01). However, excretion and fractional clearance of UA were unchanged. Sucrose and acarbose coadministration also increased pUA, but less than did sucrose alone (sucrose: 4.9 to 5.4 mg/dl; sucrose + acarbose, 4.7 to 4.9 mg/dl, p < 0.05) without changes in urinary excretion and fractional clearance of UA. Acarbose appears to attenuate the rise in pUA by sucrose ingestion by inhibiting sucrose absorption.

Acarbose alleviates rise in plasma uric acid concentration induced by sucrose ingestion.

UNLABELLED: Sucrose is divided by alpha-glucosidase into fructose and glucose, which are considered to raise plasma uric acid concentration through purine degradation and/or decreased uric acid excretion. AIMS: We investigated the effect of acarbose, an alpha-glucosidase inhibitor, on the increased plasma concentration of uric acid caused by sucrose. METHODS: 6 healthy males were studied. After an overnight fast, sucrose at 1.5 g/kg was ingested. Urine was collected 1 hour before sucrose ingestion and then twice at 1-hour intervals after ingestion. Blood was taken twice, at the midpoint of each 1-hour period. 2 weeks later, the same protocol was followed, with acarbose at 100 mg added at the beginning of the sucrose ingestion. RESULTS: Sucrose ingestion raised the plasma concentration of uric acid by 10%, whereas with the addition of acarbose the rise in plasma concentration of uric acid was reduced (p < 0.01) without changes in urinary uric acid excretion and fractional uric acid clearance. Urinary excretion and fractional clearance of oxypurines were unchanged in both experiments. CONCLUSIONS: Acarbose is considered to alleviate the rise in plasma concentration of uric acid induced by sucrose by inhibiting its absorption since no changes in uric acid excretion and fractional clearance were observed.

Relationship between insulin resistance and low urinary pH in patients with gout, and effects of PPARalpha agonists on urine pH.

Patients with gout frequently have low urinary pH, though the underlying mechanism has not been identified. Recently, nephrolithiasis has been reported to be involved with renal manifestation of metabolic syndrome. The present study was conducted to clarify the mechanism of low urinary pH in gout patients. The relationships between urine pH and factors contributing to metabolic syndrome were investigated. In addition, the effects of PPAR alpha agonists on urine pH were examined. Patients with 24-hour urine samples below a level of pH 5.5 showed higher values for factors constituting metabolic syndrome, compared with those with 24-hour urine pH equal to or greater than 5.5. Multiple regression analysis demonstrated that HOMA index was the only contributing factor to low urinary pH in gout patients, except for serum uric acid. Administrations of PPAR alpha agonists significantly raised 24-hour urine pH levels in gout patients in accordance with a reduction in serum triglyceride concentration, probably through their activities to improve insulin resistance. Our results suggest that insulin resistance plays an important role in the development of low urinary pH in patients with gout and that PPAR alpha agonist is preferable for raising urinary pH of the gout patients with hypertriglyceridemia.

Effect of beer ingestion on the plasma concentrations and urinary excretion of purine bases: one-month study.

To investigate the effect of long-term beer ingestion on the plasma concentrations and urinary excretion of purine bases, 5 healthy males participated in the present study, during which they ingested beer every evening for 30 days. Blood and 24-hour urine samples were collected in the morning one day before and 14 and 30 days after the initiation of the beer ingestion. During the beer ingestion period, the plasma concentration and the urinary excretion of uric acid were increased significantly, while uric acid clearance was not decreased. Further, purine ingestion was not significantly different throughout the study. These results suggest that production of uric acid by ethanol ingestion was the main contributor to the increased plasma uric acid. Therefore, patients with gout should be encouraged to avoid drinking large amounts of beer on a daily basis.

Effects of allopurinol on beer-induced increases in plasma concentrations and urinary excretion of purine bases (uric acid, hypoxanthine, and xanthine).

To determine the effects of allopurinol on beer-induced increases in plasma and urinary excretion of purine bases (hypoxanthine, xanthine, and uric acid), we performed three experiments on five healthy study participants. In the first experiment (combination study), the participants ingested beer (10 ml/kg body weight) eleven hours after taking allopurinol (300 mg). In the second experiment (beer-only study), the same participants ingested beer (10 ml/kg body weight) alone, while in the third experiment (allopurinol-only study), they took allopurinol (300 mg) alone. There was a two-week interval between each of the studies. Beer-induced increases in plasma concentration and urinary excretion of hypoxanthine in the combination study were markedly higher than those in the beer-only study. On the other hand, the sum of increases in plasma concentrations of purine bases in the beer-only study was greater than in the combination study, whereas the increase in plasma uridine concentration in the combination study did not differ from the beer-only study. In addition, allopurinol administration inhibited the beer-induced increase in plasma concentration of uric acid. These results suggest that abrupt adenine nucleotide degradation may increase plasma concentration and urinary excretion of hypoxanthine under conditions of low xanthine dehydrogenase activity, which is mostly ascribable to allopurinol. Further, the difference in the sum of increases in plasma concentrations of purine bases between the combination study and beer-only study was largely ascribable to a greater increase in urinary excretion of hypoxanthine in the combination study. In addition, allopurinol intake seems to be effective in controlling the rapid increase in plasma uric acid caused by ingestion of alcoholic beverages.

Effects of a fenofibrate/losartan combination on the plasma concentration and urinary excretion of purine bases.

OBJECTIVE: To assess the effects of a combination of fenofibrate and losartan on the plasma concentrations and urinary excretion of purine bases in healthy male subjects. METHODS: 5 healthy males participated in a fenofibrate plus losartan combination study. The plasma concentrations and urinary excretion of purine bases (hypoxanthine, xanthine, uric acid) were measured before and after administrations of losartan (100 mg o.d.) alone for 2 weeks, losartan and fenofibrate together for 2 weeks and fenofibrate (300 mg o.d.) alone for 2 weeks, which were given consecutively over a 6-week period. RESULTS: Losartan alone significantly reduced the serum uric acid concentration and increased uric acid excretion, whereas the combination of losartan and fenofibrate reduced serum uric acid concentrations further with a concomitant increased uric acid excretion. Fenofibrate alone also reduced plasma uric acid concentration with an increase in urinary excretion, although the effect was weak when compared with the combination treatment. The plasma concentrations and urinary excretion of oxypurines remained unchanged throughout the entire study. CONCLUSION: A combination of fenofibrate and losartan demonstrated an additive urate-lowering effect which may be beneficial in the treatment of patients with gout and hypertriglyceridemia.

Effects of long-term beer ingestion on plasma concentrations and urinary excretion of purine bases.

To investigate the long-term effects of beer ingestion on plasma concentrations of purine bases (hypoxanthine, xanthine, and uric acid), ten healthy males ingested beer (15 ml/kg body weight) every evening for three months. Blood and 24-hour urine samples were collected in the morning on one day before and one, two, and three months after starting the experiment to determine the plasma concentrations and urinary excretion of uric acid, hypoxanthine, and xanthine. Plasma concentrations and urinary excretion of uric acid, hypoxanthine, and xanthine in five of the participants that did not regularly ingest beer at a quantity of more than 15 ml/kg body weight in a single day prior to the experiment were not increased during the experimental period. In contrast, plasma concentrations and urinary excretion of uric acid were increased in five participants who regularly ingested more than 15 ml/kg body weight of beer in a single day prior to the experiment, although hypoxanthine and xanthine levels were not significantly increased during the experimental period. In both groups, uric acid clearance and purine ingestion were not significantly different throughout the study. Our results suggest that the production of uric acid caused by ethanol ingestion from beer is a significant contributor to the increase in plasma uric acid concentration in patients that regularly consume more than 15 ml/kg body weight of beer each day. Therefore, patients with gout should be encouraged to refrain from drinking large amounts of beer on a daily basis.

Effect of purine-free low-malt liquor (happo-shu) on the plasma concentrations and urinary excretion of purine bases and uridine--comparison between purine-free and regular happo-shu.

To determine whether purine-free and regular low-malt liquor beverages (happo-shu) increase the plasma concentration and urinary excretion of purine bases (hypoxanthine, xanthine, uric acid) and uridine, 6 healthy males were given regular (10 ml/kg of body weight) and purine-free happo-shu (10 ml/kg of body weight). Plasma concentration-time curves were plotted, and the areas under the curves for uric acid and total purine bases (the sum of hypoxanthine, xanthine, and uric acid) were greater in the regular than in the purine-free happo-shu ingestion experiment (both p < 0.05). In addition, the total urinary excretion of xanthine, total purine bases, and uridine was greater in the regular than in the purine-free happo-shu ingestion experiment (p < 0.05 in all cases), although the total urinary excretion of hypoxanthine and uric acid was no different between the regular and the purine-free happo-shu ingestion experiments. These results suggest that uridine contained in regular happo-shu might contribute to an increase in the urinary excretion of uridine along with ethanol, and that the purines contained in regular happo-shu may contribute to the increase in plasma concentration of uric acid due to purine degradation.

Effects of combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism.

OBJECTIVE: To assess the effect of a combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism in hypertriglyceridaemic and/or hypertensive patients with gout. METHODS: Twenty seven patients with gout were included in a fenofibrate plus anti-hyperuricaemic agents combination study, and 25 in a losartan plus anti-hyperuricaemic agents combination study. Serum uric acid concentration, uric acid clearance, and 24 hour urinary uric acid excretion were measured before and two months after the addition of fenofibrate (300 mg once daily) or losartan (50 mg once daily) to anti-hyperuricaemic agents. RESULTS: Combination therapy of fenofibrate or losartan with anti-hyperuricaemic agents, which included benzbromarone (50 mg once daily) or allopurinol (200 mg twice a day), significantly reduced serum uric acid concentrations in accordance with increased uric acid excretion. CONCLUSION: A combination of fenofibrate or losartan with anti-hyperuricaemic agents is a good option for the treatment of gout patients with hypertriglyceridaemia and/or hypertension, though the additional hypouricaemic effect may be modest.

Hyperosmolar non-ketotic diabetic syndrome associated with rhabdomyolysis and acute renal failure: a case report and review of literature.

A 64-year-old man was admitted to our hospital because of general fatigue and drowsiness. On admission, a physical examination disclosed dehydration and a laboratory investigation revealed the following values: plasma glucose, 1309 mg/dl; serum sodium, 160 mmol/l; potassium, 3.0 mmol/l; urea nitrogen, 65 mg/dl; creatinine, 2.73 mg/dl; and plasma osmolarity, 403 mOsm/kg. Urine ketone bodies were negative. A diagnosis of hyperosmolar non-ketotic diabetic syndrome was made, and hydration with an infusion of hypotonic saline (0.45%) and insulin therapy were immediately started. However, despite adequate rehydration and correction of blood glucose, his serum creatinine level increased to 3.1 mg/dl, while oliguria and myoglobinuria developed on the 4th hospital day, with serum creatine kinase increasing up to a maximum level of 16,749 IU/l, suggesting rhabdomyolysis. A final diagnosis of hyperosmolar non-ketotic diabetic syndrome associated with rhabdomyolysis and acute renal failure was made. His renal function gradually improved without hemodialysis, though acute renal failure due to rhabdomyolysis with hyperosmolar non-ketotic diabetic syndrome can sometimes be fatal. This rare case is presented along with a review of literature.

Effect of fenofibrate on plasma concentration and urinary excretion of purine bases and oxypurinol.

OBJECTIVE: To investigate whether fenofibrate increases the clearance of purine bases (hypoxanthine, xanthine, uric acid) and oxypurinol. METHODS: We administered fenofibrate (150 mg) 3 times a day for 3 days, and then allopurinol (300 mg) 4 h after the last administration of fenofibrate, to 5 healthy subjects. Ten hours later, a clearance study was done. RESULTS: Following 3 day administration of fenofibrate, fractional clearance of xanthine, uric acid, and oxypurinol increased by 41% (p < 0.05), 101% (p < 0.01), and 51% (p < 0.01), respectively, compared to baseline values, while the respective plasma concentrations decreased by 46% (p < 0.05), 46% (p < 0.05), and 19% (p < 0.05). CONCLUSION: Our results suggest that fenofibrate, fenofibric acid, or fenofibrate derivatives can increase fractional clearance of xanthine, uric acid, and oxypurinol by acting on their common renal pathways. It is suggested that the hypouricemic effect of combination therapy using allopurinol and fenofibrate may be less than additive.

An atypical case of primary renal tubular hypokalaemic metabolic alkalosis with chronic tophaceous gout.

A 55-year-old woman was referred to our ward for further evaluation of marked hyperuricaemia and suspected tophi. On physical examination, huge subcutaneous nodules were observed on the knee joints as well as a small nodule on the lateral side of the left sole. Blood chemistry showed marked hyperuricaemia (0.85 mmol/l), hypokalaemia (2.7 mmol/l) and a mild degree of renal insufficiency. Arterial blood gas analysis showed signs of metabolic alkalosis. Daily urinary uric acid excretion on a purine non-restricted diet was 8.9 mmol/day. Uric acid clearance and fractional uric acid clearance were 0.8 ml/min and 2.6%, respectively. Plasma renin activity was 21.8 ng/ml/h, and plasma angiotensin II and aldosterone concentrations were 61 and 121 pg/ml, respectively. However, pressor response to an intravenous administration of angiotensin II was normal. The urinary calcium to creatinine molar ratio was 0.069, and serum magnesium concentration was normal to supranormal. A biopsy of the subcutaneous nodule showed a typical appearance of tophus. Based on these findings, the patient was diagnosed with an atypical case of renal tubular hypokalaemic metabolic alkalosis, with marked hyperuricaemia and tophi as the initial manifestations. So far, only four cases of Bartter's syndrome with gout and/or hyperuricaemia have been described in Japan. This rare case is presented and its mechanism of hyperuricaemia discussed.

Effect of norepinephrine on the urinary excretion of purine bases and oxypurinol.

To examine whether norepinephrine affects the plasma concentrations and urinary excretion of purine bases and oxypurinol, we orally administered allopurinol (300 mg) to 5 healthy subjects and 9 hours later intravenously administered norepinephrine (12 to 20 microg/kg body weight), which causes a more than 10 mm Hg increase in diastolic pressure for 2 hours. Norepinephrine decreased the urinary excretion of uric acid by 33% (P <.01), oxypurinol by 32% (P <.01), and xanthine by 51% (P <.01), as well as the fractional clearance of uric acid by 32% (P <.01), oxypurinol by 24% (P <.05), and xanthine by 21% (P <.05) when measured 1 to 2 hours after administration. These results indicate that norepinephrine decreases the urinary excretion of uric acid, oxypurinol, and xanthine, probably via hemodynamic change. It is also suggested that the hypouricemic effect of allopurinol may be more potent than that expected in gout patients with enhanced sympathetic tone, such as in salt-sensitive hypertension.

Widespread cellular distribution of aldehyde oxidase in human tissues found by immunohistochemistry staining.

Aldehyde oxidase (EC 1.2.3.1) is a xenobiotic metabolizing enzyme that catalyzes a variety of organic aldehydes and N-heterocyclic compounds. However, its precise pathophysiological function in humans, other than its xenobiotic metabolism, remains unknown. In order to gain a better understanding of the role of this enzyme, it is important to know its exact localization in human tissues. In this study, we investigated the distribution of aldehyde oxidase at the cellular level in a variety of human tissues by immunohistochemistry. The enzyme was found to be widespread in respiratory, digestive, urogenital, and endocrine tissues, though we also observed a cell-specific localization in the various tissues studied. In the respiratory system, it was particularly abundant in epithelial cells from the trachea and bronchium, as well as alveolar cells. In the digestive system, aldehyde oxidase was observed in surface epithelia of the small and large intestines, in addition to hepatic cells. Furthermore, the proximal, distal, and collecting tubules of the kidney were immunostained with various intensities, while glomerulus tissues were not. In epididymus and prostate tissues, staining was observed in the ductuli epididymidis and glandular epithelia. Moreover, the adrenal gland, cortex, and notably the zona reticularis, showed strong immunostaining. This prevalent tissue distribution of aldehyde oxidase in humans suggests some additional pathophysiological functions besides xenobiotic metabolism. Accordingly, some possible roles are discussed.

Decreased activities of lipoprotein lipase and hepatic triglyceride lipase in patients with gout.

Postheparin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities were measured in 30 male primary gout patients as well as in control subjects. The activities of these lipolytic enzymes were significantly decreased in the patients as compared with the controls (gout v control; LPL, 5.4 +/- 0.4 v 7.9 +/- 0.9 U; HTGL, 14.6 +/- 2.0 v 17.9 +/- 3.4 U) when matched with serum triglyceride concentration. Further, LPL activity was negatively correlated with serum- and very-low-density lipoprotein (VLDL)-triglyceride in gout patients, while that of HTGL was negatively correlated with low-density lipoprotein (LDL)-triglyceride in both gout patients and control subjects. These results suggest that decreased activities of LPL and HTGL may contribute, in part, to the increased concentrations of serum-, VLDL-, and LDL-triglyceride seen in gout patients, leading to a higher risk for coronary atherosclerotic diseases in gout.

Spot urine uric acid to creatinine ratio used in the estimation of uric acid excretion in primary gout.

OBJECTIVE: Uric acid overexcretion in patients with gout is frequently assessed by the measurement of 24 hour urinary uric acid excretion, which is cumbersome with ambulatory patients, and requires accurate timing and complete collection of the specimen. We assessed whether uric acid to creatinine ratio (Uua/Ucr) in spot urine is useful for the estimation of uric acid overexcretion in patients with gout. METHODS: One hundred thirty male patients with gout and 33 non-gout male control subjects were studied. Early morning urine and/or a portion of 24 h collected urine (24 h urine) were used as spot urine samples. Uric acid overexcreters were defined as those with a 24 h urinary uric acid excretion > or = 1000 mg/day, while uric acid underexcreters were defined as those with uric acid clearance < 6 ml/min. RESULTS: There was a significant relationship between 24 h urinary uric acid excretion and early morning urine Uua/Ucr in patients with gout, while no such relationship was observed in controls. No significant difference in Uua/Ucr was observed between patients with gout and controls, or in Uua/Ucr between gout uric acid overexcreters and underexcreters in early morning urine. A significant difference in this value was observed between the 2 groups in the 24 h urine specimens. Although the diagnostic accuracy of gout uric acid overexcretion was 87.2% using early morning urine and 89.6% using 24 h urine, the sensitivity of gout uric acid overexcretion was only 25.0% when using early morning urine and 25.0% when using 24 h urine, when the cutoff value of Uua/Ucr was 0.63 and 0.64, respectively. CONCLUSION: Uua/Ucr using spot urine, especially early morning urine, is not an accurate indicator of uric acid overexcretion in patients with gout.

Increased visceral fat accumulation further aggravates the risks of insulin resistance in gout.

We performed the present study to determine the degree of visceral fat accumulation and incidence of visceral fat obesity in 138 gout patients who were classified as overexcretion type (n = 53) and underexcretion type (n = 85) by their levels of uric acid clearance and urinary uric acid excretion. We also investigated the relationship between visceral fat accumulation and insulin resistance expressed by the homeostasis model assessment (HOMA) index. Visceral fat area (VFA)/surface body area (SBA) was significantly increased in patients with gout as compared with control subjects (79.7 +/- 30.8 cm(2)/m(2) v 65.1 +/- 24.1 cm(2)/m(2), P <.001). It was also shown that VFA/SBA in the gout overexcretion group was significantly increased as compared with the gout underexcretion group (88.3 +/- 32.8 cm(2)/m(2) v 74.3 +/- 28.3 cm(2)/m(2), P <.01). Although the incidence of visceral fat obesity (VFO) was not different between gout patients and control subjects, the incidence of VFO was significantly higher in the gout overexcretion type than the gout underexcretion type (19 of 53 v 11 of 85, P <.01). Further, there was a significant relationship between visceral fat area and HOMA index. Gout patients possess some factors that are included in the insulin resistance syndrome, irrespective of the presence of VFO, and the insulin resistance risk factors observed in gout become more prominent when it is complicated with VFO. Our results suggest that gout patients, especially the overexcretion type who have greater levels of visceral fat accumulation, may be more vulnerable to atherosclerotic diseases.